Using a cell lineage approach we plan to study cell aging in two model systems. Digitalized data obtained by image processing of time lapse films will be used to analyze changes in morphology, motility, cell division cycle, social behavior and biochemistry which occur as cell doubling level increases in clones of WI-38 normal and transformed cells. A new approach for the identification and measurement of chemical species in space and time in individual living cells will be developed. Clonal histories of the accumulation and distribution of pigments detectable by laser fluorescence will be filmed and analyzed. In a second system aging of cells of the immune system will be studied with respect to similar variables. In carrying out specific immunological functions these cells depend on movement and social interactions. We will test whether cells which escape aging are blocked at a specific level of differentiation or whether they have undergone a genetic change. We will carry out intraclonal studies at constant and variable cell densities to determine the extent and possible causes of aging heterogeneity in WI-38 cell populations. Using chemical mutagens we shall also try to find cells of normal karyotype which have escaped aging. Among the hypotheses we wish to test is that cells leave cycle because of a "defect" in the actin-myosin network thought to be associated with motility. Changes in the actin-myosin network as well as in morphology and cell dynamics which occur in the course of the cell cycle will be distinguished from those which change undirectionally in aging cells. Comparison with cells which escape aging will be made.